In vitro antitumor activities of new synthetic bistetrahydrofuran derivatives as analogs of Annonaceous acetogenins.
We investigated the in vitro antitumor activities toward mouse and human cell lines of optically active synthetic bistetrahydrofuran (bis-THF) derivatives as analogs of Annonaceous acetogenins, which contain bis-THF, long unbranched alkyl chains, hydroxyl groups, and an alpha, beta-unsaturated gamma-lactone. These bis-THF derivatives were synthesized in a stereocontrolled manner, and have several modified structures at the alkyl side chains. We found that: 1) the unsaturated gamma-lactone contributes to high potency in combination with the other less-functionalized alkyl chain, 2) the same absolute configuration of the bis-THF skeleton as that of the natural products produces more potent activity than the counterpart, 3) the alkyl chains and hydroxyl groups are crucial for exhibiting antitumor activity, 4) hydroxyl groups adjacent to the bis-THF skeleton may be replaced by amino or acylamino groups.
Sasaki
S
S
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Maruta
K
K
Naito
H
H
Maemura
R
R
Kawahara
E
E
Maeda
M
M
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology*; D005663:Furans / Q000138:chemical synthesis*; D006801:Humans; D017665:Hydroxyl Radical / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis*; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D007783:Lactones; D010936:Plant Extracts; C096951:annonacin-A-one; D017665:Hydroxyl Radical; C018674:tetrahydrofuran; D015107:4-Butyrolactone